1. Field
The present disclosure generally relates to the field of iontophoresis, and in particular, to an iontophoresis device capable of preventing or suppressing an undesirable electrode reaction in an electrode assembly.
2. Description of the Related Art
lontophoresis involves electrically driving an active agent that has dissociated into positive or negative ions in solution by using a voltage to transdermally transfer the active agent into a subject, and has advantages such as reduced patient burden and excellent controllability of the amount of the active agent to be administered.
FIG. 9 is an explanatory view that shows a basic configuration of an iontophoresis device.
The iontophoresis device of FIG. 9 comprises: an active electrode assembly 110 having an electrode 111 and an active agent solution reservoir 114 that holds a solution of an active agent dissociated into positive or negative active agent ions (active agent solution); a counter electrode assembly 120 having an electrode 121 and an electrolyte solution reservoir 122 that holds an electrolyte solution; and an electric power source 130 including two terminals connected to the electrodes 111 and 121. An electrical potential or voltage having the same polarity as that of active agent ions is applied to the electrode 111 and an electrical potential or voltage having a polarity opposite to that of the active agent ion is applied to the electrode 121 in a state where the active agent solution reservoir 114 and the electrolyte solution reservoir 122 are brought into contact a biological interface of a subject. The active agent ions are thus administered to the subject.
Problems that may occur in such an iontophoresis device include a variety of electrode reactions occurring in the electrode assemblies 110 and 120.
For example, when using a cationic drug that dissociates into positive active agent ions, hydrogen ions or oxygen gas may be generated at the electrode 111 and hydroxide ions or hydrogen gas may be generated at the electrode 121 due to the electrolysis of water. In addition, the active agent causes a chemical reaction near the electrode 111 to change depending upon the kind of the active agent and the energization conditions. Furthermore, when the active agent solution reservoir 114 contains chlorine ions, a chlorine gas or hypochlorous acid may be generated.
Similarly, when using an anionic drug that dissociates into negative active agent ions, hydroxide ions or a hydrogen gas may be generated at the electrode 111 and hydrogen ions or an oxygen gas may be generated at the electrode 121 due to the electrolysis of water. In addition, the active agent causes a chemical reaction near the electrode 111 to change depending upon the kind of the active agent and the energization conditions. Furthermore, when the electrolyte solution reservoir 122 contains chlorine ions, a chlorine gas or hypochlorous acid may be generated.
Energization from the electrode 111 or 121 to the active agent solution or the electrolyte solution may be inhibited when a gas as described above is generated in the electrode assembly 110 or 120. When hydrogen ions, hydroxide ions, or hypochlorous acid are generated in the electrode assembly 110 or 120, they may transfer to a biological interface and have a detrimental effect on a subject. In addition, the alteration of an active agent may cause undesirable conditions such as the inability to obtain an initial drug effect and the production of a toxic substance.
U.S. Pat. No. 4,744,787 discloses, as an iontophoresis device capable of solving such problems as described above, an iontophoresis device in which a silver electrode is used as an anode and a silver chloride electrode is used as a cathode.
In the disclosed device, a reaction preferentially occurs where silver in the anode is oxidized by energization to become insoluble silver chloride, while silver chloride is reduced at the cathode to become metallic silver. As a result, the generation of various gases and the production of various ions due to such electrode reactions as described above can be suppressed.
However, it is difficult to prevent the dissolution of the silver electrode during storage of the iontophoresis device. In particular, when the device is intended for use administering a cationic drug, the amount of applicable drug types is extremely limited. In addition, morphological change upon production of silver chloride from the silver electrode is large. Therefore, special consideration must be given in order to prevent such morphological change from affecting the properties of the device. As a result, a problem may arise in that a severe restriction is imposed on the configuration of the device (for example, it may be impossible to adopt a laminate structure). Furthermore, the iontophoresis device is unable to solve the problem of the alteration of the active agent upon energization.
JP 3040517 B discloses an iontophoresis device shown in FIG. 10 as another iontophoresis device capable of solving the problems described above.
Referring to FIG. 10, the iontophoresis device comprises: an active electrode assembly 210 including an electrode 211, an electrolyte solution reservoir 212 holding an electrolyte solution in contact the electrode 211, an ion exchange membrane 213 of a second polarity, the ion exchange membrane 213 being placed on the front surface side of the electrolyte solution reservoir 212, an active agent solution reservoir 214 holding an active agent solution containing active agent ions of a first polarity, the active agent solution reservoir 214 being placed on the front surface side of the ion exchange membrane 213, and an ion exchange membrane 215 of the first polarity, the ion exchange membrane 215 being placed on the front surface side of the active agent solution reservoir 214; and a counter electrode assembly 220 and an electric power source 230 similar to those shown in FIG. 9.
In the iontophoresis device, the electrolyte solution and the active agent solution are partitioned by the second ion exchange membrane 213 of the second polarity. As a result, the composition of the electrolyte solution can be selected independently of the active agent solution. An electrolyte solution that does not contain chlorine ions can thus be used. In addition, the selection of an electrolyte having a lower oxidation or reduction potential than the electrolysis of water as the electrolyte in the electrolyte solution can suppress the production of oxygen gas, hydrogen gas, hydrogen ions, and hydroxide ions resulting from the electrolysis of water. Alternatively, the use of a buffer electrolyte solution into which a plurality of electrolytes are dissolved may suppress changes in pH due to the production of hydrogen ions or hydroxide ions. Furthermore, the transfer of active agent ions to the electrolyte solution reservoir is blocked by the second ion exchange membrane, thus solving a problem where the active agent alters due to a chemical reaction occurring when the device is turned on.
However, the iontophoresis device disclosed in JP 3040517 B comprises a large number of members, and the electrolyte solution reservoir 212 and the active agent solution reservoir 214 must each be handled in a wet state (a state with high water content). Therefore, a problem arises in that automated device production and mass production of the device may be difficult, and may not result in production cost reductions.
Other references considered include “KS Kagaku Senmonsho Dodensei Kobunshi” edited by Naoya Ogata, Kodansha, published January, 1990, and “Shin Zairyou series Dodensei Koubunshi no Saishin Ouyou Gijutsu” written by Yukuo Kobayashi, CMC Publishing CO., LTD., published July, 2004